Sunday, April 13, 2014

The complex
I of the mitochondrial respiratory chain may also be referred as NADH:ubiquinone
oxidoreductase or NADH dehydrogenase. It is the largest of the four respiratory
chain complexes, having a higher size than a ribosome.

It is L-shaped, with 60
transmembrane domains and a hydrophilic peripheral region that contains the
binding site of NADH and the redox centers. Complex I is composed by 44
distinct polypeptide chains, among them it is found a flavoprotein (with FMN as
cofactor) and 8 iron-sulfur centers. Of these 44 proteins, 7 are encoded by
mitochondrial DNA, while the remainder are encoded by nuclear DNA.

From the
functional point of view, the complex I receives electrons from NADH and
transfers them to ubiquinone. When I talk about NADH, I am referring to any
mitochondrial NADH molecules, despite their origin, because NADH is associated
reversibly to dehydrogenases. That means, after being formed inside the
mitochondria, NADH can diffuse to reach the complex I, where it delivers the 2
electrons that it carries. During the transport of electrons along this complex,
they are transferred to a protein which has as a FMN cofactor, originating FMNH2.
Then, the electrons pass through various centers of iron-sulfur (Fe - S), until
they reach the ubiquinone (Q ), which receives 2 electrons at a time, turning
into ubiquinol (QH2).

During the
transport of electrons along the complex I, there are small quantities of
energy that are being released, which could not be used alone to produce ATP.
Thus, our body retains some of that energy by creating a gradient of H+.
That is, the energy that is released is used to actively transport H+
from the matrix to the intermembrane space. In the case of complex I, for every
2 electrons passing through it, 4 protons are pumped into the intermembrane
space.

The
chemical equation describing the action of complex I is:

NADH + 5H+(matrix) + Q → NAD+ + QH2
+ 4H+ (intermembrane space)

There are several
diseases caused by mutations in genes encoding components of complex I, namely,
the Leber’s Hereditary Optic Neuropathy and Leigh syndrome.